To find lead compounds for drug discovery programs, large numbers of compounds are often screened for their activity as enzyme inhibitors or receptor agonists/antagonists. Large libraries of compounds are needed for such screening. As a result of developments in this field, it is now possible to simultaneously produce combinatorial libraries containing hundreds of thousands of small molecules for screening. With the availability of such libraries, however, has come a need for large scale, rapid screening methods. In the context of these methods, it has proven advantageous to perform a plate to plate transfer employing the 1536-well plate described in PCT Application Ser. No. PCT/US98/00494 entitled Multi-Well Plate, filed Jan. 8, 1998 and incorporated by reference herein, or employing other plates containing a large number of samples in a large number of low volume wells. Such plates are secured in a facing alignment in a centrifugation bucket and centrifuged to effect transfer.
When two plates are secured in a centrifugation bucket, an interstice exists at the contact surface between the plates, providing a possible path for liquid flow between the plates and along the surfaces of the plates. Capillary action contributes to this flow. Also contributing to this flow are force components produced during centrifugation which act parallel to the interstice between the plates. Liquid flow along the surfaces of the plates is highly undesirable because it allows contamination of the contents of one well by liquid lowing from another well, and because it allows loss of material as liquid flows out of the lates through the interstice between the plates.
In a typical centrifugation bucket of the prior art, the centrifugation bucket is mounted on a centrifuge rotor by a hinge, allowing the bucket to pivot about a single axis in response to the forces of centrifugation. This allows the plates to be held parallel to the axis of rotation of the centrifuge once operational speed has been achieved. The only force produced by centrifugation during this time is a force acting normal to the surfaces of the plates. However, during starting and stopping of the centrifuge, tangential force components exist which act parallel to the surfaces of the plates and thus parallel to the interstice between the plates. These forces exist while the centrifuge accelerates from rest to its operating speed, and while the centrifuge decelerates from its operating speed to a resting position, and are produced by changes in rotational speed. The tangential forces tend to produce flow of liquid in the interstice between the plates and parallel to the surfaces of the plates. This presents a risk of contamination and loss of material.
As noted above, a typical centrifugation bucket according to the prior art comprises a yoke which is free to pivot around a single hinge. When the centrifugation bucket is at rest, the yoke is in a resting horizontal position. When the centrifugation bucket is placed in a centrifuge and is accelerated to operating speed, the yoke swings upward under the influence of the centrifugal forces produced by the rotation of the centrifuge, and is held parallel to the axis of rotation by these centrifugal forces. The force produced by centrifugation under these circumstances is the normal force, which acts perpendicular to the plates. However, as the centrifuge is accelerated or decelerated, tangential forces acting parallel to the surfaces of the plates also materialize, and contribute to liquid flow between the plates. Because the centrifugation bucket pivots about a single hinge, it lacks sufficient freedom of movement to respond to both the normal force and the tangential force exerted during the centrifuging process.
There exists, therefore, a need in the art for an improved centrifugation bucket for use in centrifuging multi-well plates, which allows the plates to pivot so as to allow maximization of forces acting perpendicular to the plates and minimization of forces acting parallel to the plates.